Researchers Identify A Protein Critical For T Cell Development And Activation

IOWA CITY, Iowa -- Scientists at the University of Iowa have just added a piece to the puzzle of immunesytem activation. Stimulation of the immune system involves more than a binary on-off response. When a foreign body attaches to a T cell receptor, it sets off a chain of biochemical reactions that lead to immune system activation.

Gary Koretzky, M.D. Ph.D., UI Kelting Professor of Rheumatology, reports that the protein SLP-76 appears to be critical for the development and activation of T cells, an important part of the immune system. This finding is reported in the July 17 issue of Science magazine.

The finding provides scientists with a better understanding of the basic biology of immune system activation, which is critical to understanding immunodeficiency disorders and autoimmune diseases, such as rheumatoid arthritis, diabetes and systemic lupus.

Activation of the specialized receptor for foreign substances, the T cell antigen receptor, starts a cascade of biochemical events that lead to T cell activation. This cascade involves the activation of proteins which then activate other proteins in succession until the T cell itself is stimulated. The proteins in this series, or pathway, are referred to as second messengers. Koretzky's interest in learning more about this second messenger signaling pathway and how the proteins communicate with each other led to identification of the protein SLP-76in 1995.

"What is striking about this molecule is that it isn't a an enzyme like most of the other molecules in the signaling pathway. It is an adapter protein," Koretzky said. Adapter proteins bind proteins together. They don't catalyze reactions like enzymes, but they can enhance reactions by creating a bridge that brings proteins together.

"Our thinking was that perhaps SLP-76 played an important role in lymphocyte (white blood cell) activation," Koretzky said. He and his colleagues tested this hypothesis by manipulating the gene that produces the SL

Contact: L.E. Ohman
(319) 335-6660
University of Iowa

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